Small Cell Lung CancerPhase 1/2NCT02514447
Trilaciclib (G1T28) in Patients With Previously Treated Extensive Stage SCLC Receiving Topotecan Chemotherapy
A Phase 1/2 study testing Trilaciclib and Topotecan in people with Small Cell Lung Cancer, run by G1 Therapeutics, Inc. at 50 sites in 8 countries.
Trial summary
This was a study to investigate the potential clinical benefit of trilaciclib (G1T28), a Cyclin Dependent Kinase (CDK) 4/6 inhibitor, in preserving the bone marrow and the immune system, in order to decrease chemotherapy-induced myelosuppression and improve anti-tumor efficacy when administered prior to topotecan in… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Small Cell Lung Cancer
- What is being tested?
- Trilaciclib and Topotecan
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 123 participants
- Where
- 50 sitesin 8 countries
- Study dates
- 5 Oct 2015to 4 Oct 2021
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female subjects aged ≥18 years
- Confirmed diagnosis of SCLC by histology or cytology, preferably including the presence of neuroendocrine features by immunohistochemistry
- Progression during or after prior first- or second-line chemotherapy and eligible to receive topotecan therapy
- At least 1 target lesion that is measurable by RECIST, Version 1.1
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2
- Adequate organ function
Who cannot join
- Presence of brain metastases requiring immediate treatment with radiation therapy or steroids.
- Uncontrolled ischemic heart disease or uncontrolled symptomatic congestive heart failure
- Known history of stroke or cerebrovascular accident within 6 months prior to enrollment
- Other uncontrolled serious chronic disease or conditions that in the investigator's opinion could affect compliance or follow-up in the protocol
- Concurrent radiotherapy to any site or radiotherapy within 2 weeks prior to enrollment or previous radiotherapy to the target lesion sites
- Receipt of any systemic chemotherapy regimen within 4 weeks prior to enrollment or a noncytotoxic investigational medication within 2 weeks prior to enrollment
- History of topotecan treatment for SCLC
Trial locations and contacts
50 sites in 8 countries.
50 sites in 8 countries
United States35 sites
AnMed Health
Anderson, South Carolina, 29621
University Cancer and Blood Center, LLC
Athens, Georgia, 30607
Emory University
Atlanta, Georgia, 30322
Northside Hospital - Georgia Cancer Specialists
Atlanta, Georgia, 30341
Gabrail Cancer Center
Canton, Ohio, 44718
Memorial Hospital - University of Colorado Health
Colorado Springs, Colorado, 80909
Compassionate Cancer Care Medical Group, Inc.
Corona, California, 92879
Texas Oncology- Baylor Charles A. Sammons Cancer Center
Dallas, Texas, 75246
Rocky Mountain Cancer Centers
Denver, Colorado, 80218
North Shore Hematology Oncology Associates PC
East Setauket, New York, 11733
Virginia Cancer Specialists
Fairfax, Virginia, 22031
University of Colorado Health, Oncology Clinical Research Northern Region
Fort Collins, Colorado, 80528
Florida Cancer Specialists - South
Fort Myers, Florida, 33916
Greenville Health System
Greenville, South Carolina, 29605
Genesis Cancer Center
Hot Springs, Arkansas, 71913
M.D. Anderson
Houston, Texas, 77030
Millennium Oncology
Houston, Texas, 77090
Saint Luke's Cancer Institute
Kansas City, Missouri, 64111
Hanna Cancer Associates - University of Tennessee
Knoxville, Tennessee, 37920
Norris Cotton Cancer Center
Lebanon, New Hampshire, 03756
Southwest Cancer Center
Lubbock, Texas, 79415
Meharry Medical College
Nashville, Tennessee, 37208
Sarah Cannon Research Institute
Nashville, Tennessee, 37232
Virginia Oncology Associates
Norfolk, Virginia, 23502
Oklahoma University - Peggy and Charles Stephenson Cancer Center
Oklahoma City, Oklahoma, 73117
Highlands Oncology Group
Rogers, Arkansas, 72758
Sutter Medical Group
Sacramento, California, 95816
Guthrie Medical Group, PC
Sayre, Pennsylvania, 18840
Gibbs Cancer Center
Spartanburg, South Carolina, 29303
Florida Cancer Specialists - North
Tavares, Florida, 32778
Texas Oncology
Tyler, Texas, 75702
The University of Texas Health Science Center at Tyler
Tyler, Texas, 75708
Northwest Cancer Specialists, P.C.
Vancouver, Washington, 98684
The Oncology Institute of Hope and Innovation
Whittier, California, 90603
Regional Medical Oncology Center
Wilson, North Carolina, 27893
Serbia5 sites
Clinic for Pulmology, Clinical Centre of Serbia
Belgrade, 11000
Clinical Hospital Centre Bezanijska Kosa
Belgrade, 11000
Oncology and Radiology Institute of Serbia
Belgrade, 11000
Institute for Pulmonary Diseases of Vojvodina Clinic for Thoracic Oncology
Kamenitz, 21204
Clinical Center Nis, Clinic for Lung Diseases
Niš, 18204
Croatia3 sites
Clinical Hospital Centre Osijek
Osijek, 31000
University Clinical Hospital Centre " Sestre Milosrdnice"
Zagreb, 10000
University Hospital Centre Zagreb, Clinic For Pulmonary Diseases Jordanovac
Zagreb, 10000
Bosnia and Herzegovina2 sites
University Clinical Centre Banja Luka
Banja Luka, 78000
University Clinical Centre Sarajevo
Sarajevo, 71000
Slovakia2 sites
VOU Department of Radiotherapy and Oncology
Košice, 04191
POKO POPRAD, s.r.o.
Poprad, 05801
North Macedonia1 site
University Clinic of Radiotherapy and Oncology Skopje
Skopje, 1000
Slovenia1 site
University Clinic of Respiratory and Allergic Diseases Golnik
Golnik
About this study
Official title: Phase 1b/2a Safety and Pharmacokinetic Study of G1T28 in Patients With Previously Treated Extensive Stage Small Cell Lung Cancer (SCLC) Receiving Topotecan Chemotherapy
This was a study to investigate the potential clinical benefit of trilaciclib (G1T28), a Cyclin Dependent Kinase (CDK) 4/6 inhibitor, in preserving the bone marrow and the immune system, in order to decrease chemotherapy-induced myelosuppression and improve anti-tumor efficacy when administered prior to topotecan in patients previously treated for extensive-stage SCLC.
The study consisted of 2 parts: a limited open-label, dose-finding portion (Part 1), and a randomized double-blind portion (Part 2). Both parts included 3 study phases: Screening Phase, Treatment Phase, and Survival Follow-up Phase. The Treatment Phase began on the day of first dose with study treatment and completes at the Post-Treatment Visit.
Read the detailed description
Overall, up to 130 patients were planned to be enrolled in the study. In Part 1, approximately 40 patients were planned to be enrolled, assuming 9 to 10 cohorts. Part 1 was open-label, and no randomization or blinding was required. In Part 2A, approximately 45 patients were to be enrolled and randomly assigned (2:1) to trilaciclib (240 mg/m2) and topotecan (0.75 mg/m2) or placebo and topotecan (1.5 mg/m2). In Part 2B, approximately 45 patients were to be enrolled and randomly assigned (2:1) to trilaciclib (240 mg/mg2) and topotecan (1.5 mg/m2) or placebo and topotecan (1.5 mg/m2).
Patients who received placebo in Part 2A and Part 2B were to be combined into a single placebo group for the analysis to compare with trilaciclib+topotecan 1.5 mg/m2 with placebo + topotecan 1.5 mg/m2 (proximately 30 per treatment group).
The sample size calculation was to demonstrate the superiority of trilaciclib + topotecan 1.5 mg/m2 over placebo + topotecan 1.5 mg/m2 with respect to at least 1 of the primary endpoints. The overall type I error rate was 1-sided 0.10. Using the most conservative Bonferroni procedure for the 2 primary endpoints, a 1-sided individual type I error rate 0.10/2=0.05 was assigned to each outcome variable (DSN in Cycle 1 and occurrence of SN) in the sample size calculation. Assuming a common standard deviation of 2.5, a difference in the duration of SN in Cycle 1 of at least 2 days between the treatment groups, a sample size of 28 per arm was required to have 90% power to detect the assumed treatment effect. For occurrence of SN, assuming the event rate was 45% for placebo group, to detect an absolute reduction of 37% by trilaciclib group with 90% power would require a sample size of at least 29 per arm. Thus, 30 per arm was needed to ensure 90% power to detect assumed treatment effect for DSN in Cycle 1 and occurrence of SN. All calculations were carried out using the POWER procedure in SAS®, Version 9.4 procedure in SAS®, Version 9.4 or higher.
The results from endpoints that were commonly collected at Part 1 and part 2 are presented together in this report.
The posted results represent the final results of Study G1T28-03, a Phase 1b/2a safety and pharmacokinetic (PK) study of trilaciclib (G1T28) in patients with previously treated extensive-stage small cell lung cancer (SCLC) receiving topotecan chemotherapy in the second/third-line (2/3L) setting. The final myelopreservation efficacy results for both parts and exposure for Part 1 are from database lock 1 (data cut-off [DCO] for Primary Completion Date [PCD] 28 September 2018). The final anti-tumor efficacy (BOR, DOR, PFS) for both parts, final overall survival for Part 1 and exposure data from Part 2 are from a second database lock 2 (DCO 31 May 2019) and the final overall survival for Part 2 and safety (adverse events) are through the end of the study on October 4, 2021 which resulted in the final database lock (DCO 01 Nov 2021).
The maximum time frames provided reflect the time from when the first patient could be evaluated for an endpoint (ie. date of first dose of first patient) to the time when the data from both parts presented for that endpoint was considered final.
- Conditions
- Small Cell Lung Cancer
- Being tested
- Trilaciclib, Placebo, Topotecan
- Keywords
- SCLC, CDK4/6 Inhibitor
- Medical subject headings
- Small Cell Lung Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TrilaciclibDrug
Also called G1T28, CDK 4/6 inhibitor
PlaceboDrug
TopotecanDrug
| Study group | Role | What they receive |
|---|---|---|
| Placebo + Topotecan 1.5 mg/m² - Parts 2a and 2b | Experimental | Patients in Parts 2a and 2b were randomized 1:2 to placebo. Patients received placebo administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle.
Following administration of placebo on Days 1 to 5, patients received IV topotecan (1.5 mg/m²). Receives: Drug: Placebo; Drug: Topotecan |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Part 2a | Experimental | Patients in Part 2a were randomized 2:1 to trilaciclib. Patients received trilaciclib (240 mg/m²) administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle.
Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Receives: Drug: Trilaciclib; Drug: Topotecan |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.5 mg/m² - Part 2b | Experimental | Patients in Part 2b were randomized 2:1 to trilaciclib. Patients received trilaciclib (240 mg/m²) administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle.
Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.5 mg/m²). Receives: Drug: Trilaciclib; Drug: Topotecan |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.5 mg/m² - Cohort 1- Part 1 | Experimental | Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle.
Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.50 mg/m²). Receives: Drug: Trilaciclib; Drug: Topotecan |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.25 mg/m² - Cohort 2- Part 1 | Experimental | Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle.
Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.25 mg/m²). Receives: Drug: Trilaciclib; Drug: Topotecan |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 0.75 mg/m² - Cohort 3- Part 1 | Experimental | Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle.
Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Receives: Drug: Trilaciclib; Drug: Topotecan |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Cohorts 4 and 6- Part 1 | Experimental | Patients received trilaciclib (240 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle.
Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Receives: Drug: Trilaciclib; Drug: Topotecan |
| Trilaciclib (G1T28) 280 mg/m² + Topotecan 0.75 mg/m² - Cohort 5- Part 1 | Experimental | Patients received trilaciclib (280 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle.
Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Receives: Drug: Trilaciclib; Drug: Topotecan |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.0 mg/m² - Cohort 7- Part 1 | Experimental | Patients received trilaciclib (240 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle.
Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.0 mg/m²). Receives: Drug: Trilaciclib; Drug: Topotecan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Duration of Severe (Grade 4) Neutropenia in Cycle 1
Duration of severe neutropenia (DSN; days) was defined as the number of days from the date of the first ANC value of <0.5 × 10^9/L observed between start of cycle and end of cycle to the date of the first ANC value ≥0.5 × 10^9/L that met the following criteria: (1) occurred after the ANC value of <0.5 × 10^9/L and (2) no other ANC values <0.5 × 10^9/L occurred between this day and end of cycle. DSN is set to 0 for patients who did not experience SN in a cycle, including those who were randomized but never treated. Data from unscheduled visits and the actual assessment date (rather than visit date) were included in the derivation.
Measured: Evaluated for Cycle 1 (i.e., from date of first dose of study drug (Part 1)/randomization (Part 2) to the end of Cycle 1, each cycle = 21 days)
Occurrence of Severe (Grade 4) Neutropenia
Number of Participants with severe (Grade 4) neutropenia (SN) was a binary variable. If a patient had at least 1 absolute neutrophil count value <0.5 × 10^9/L during the Treatment Period, the patient was assigned as Yes to the occurrence of SN; otherwise, it was No.
Measured: During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days).
Assess the Dose Limiting Toxicities (DLTs) of G1T28/Trilaciclib Administered With Topotecan in Part 1
The percentage of patients experiencing DLTs in Part 1 of the study in each cohort, including:
- Absolute neutrophil count (ANC) < 0.5 × 10^9/L lasting for ≥ 7 days
- ≥ Grade 3 neutropenic infection/febrile neutropenia
- Grade 4 thrombocytopenia or ≥ Grade 3 thrombocytopenia with bleeding
- Unable to start next cycle of chemotherapy due to lack of recovery to an ANC ≥ 1.5 × 10^9/L and platelet count ≥ 100 × 10^9/L; a delay of up to 1 week from the scheduled start of Cycle 2 is allowed for recovery of ANC and platelet count, and is not considered a DLT
- ≥ Grade 3 nonhematologic toxicity (nausea, vomiting, and diarrhea failing maximal medical management; fatigue lasting for > 72 hours)
Measured: Evaluated for Cycle 1 (i.e., from date of first dose of study drug (Part 1) to the end of Cycle 1, each cycle = 21 days)
Secondary outcomes (20)
Pharmacokinetic Profile for Trilaciclib (G1T28) When Administered With Topotecan
Maximum concentration (Cmax) of trilaciclib (G1T28) when administered with topotecan
Measured: Part 1 of the study during Cycle 1 Day 4 : predose, 0.5, 1, 1.5, 2, 2.5, 3, 4.5, 6.5, 8.5 (optional), and 24.5 hours post dose. Part 2 of the study during Cycle 1 Day 4 : predose, 0.5, 1, between 3 to 4 hours and between 5.5 to 6.5 hours post dose.
Progression Free Survival (PFS)
Median time (months) and 95% CI from date of first dose of study drug/randomization until date of documented disease progression or death due to any cause.
Investigators followed the Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1 guidelines for tumor assessments to determine progression. Progressive Disease (PD) was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).
Measured: From date of first dose of study drug (Part 1)/randomization (Part 2), until date of documented disease progression or death due to any cause (evaluated up to a maximum of 1335 days).
Overall Survival (OS)
Median time (months) and 95% CI from date of first dose date of study drug/randomization until date of death. Patients who do not die during the study will be censored at the date last known to be alive.
Measured: From date of first dose of study drug (Part 1)/randomization (Part 2) until the date of death due to any cause (evaluated up to a maximum of 2220 days).
Assess the Hematologic Profile of G1T28/Trilaciclib Administered With Topotecan
The weekly event rate of Major Adverse Hematologic Events (MAHE) events
Measured: During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days).
Tumor Response Based on RECIST, Version 1.1
The percentage of patients who fall into each category of Best overall response (BOR) as defined by RECIST, Version 1.1.
Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions.
Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions.
Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
When no imaging/measurement is done, the patient is not evaluable (NE); and if only a subset of lesion measurements are made, usually the case is also considered NE.
Measured: From date of first dose of study drug (Part 1)/randomization (Part 2) until the occurrence of progressive disease, withdrawal of consent, or initiation of subsequent anti-cancer therapy, (assessed up to a maximum of 1335 days).
Occurrence of RBC Transfusions
Percentage of patients requiring a RBC transfusion on/after week 5
Measured: During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1056 days).
Need for Treatment With Hematopoietic Growth Factors
Percentage of patients requiring G-CSF administration.
Measured: During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days).
Chemotherapy Cycles and Modifications Overall
Average exposure and cycle modifications in chemotherapy (topotecan)
Measured: During the treatment period. From date of first dose, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to a maximum of 1335 days).
Pharmacokinetic Profile for Topotecan When Administered With Trilaciclib (G1T28)
Maximum concentration (Cmax) of topotecan when administered with trilaciclib (G1T28)
Measured: Part 1 of the study during Cycle 1 Day 4 : predose, 0.5, 1, 1.5, 2, 2.5, 3, 4.5, 6.5, 8.5 (optional), and 24.5 hours post dose. Part 2 of the study during Cycle 1 Day 4 : predose, 0.5, 1, between 3 to 4 hours and between 5.5 to 6.5 hours post dose.
Duration of Response (DOR)
The median months and 95% CIs of duration of response.
Measured: From date of first dose of study drug (Part 1)/randomization (Part 2) until the occurrence of progressive disease, withdrawal of consent, or initiation of subsequent anti-cancer therapy, (assessed up to a maximum of 1335 days).
Occurrence of Intravenous (IV) Antibiotic Use
Percentage of patients requiring systemic/IV antibiotics
Measured: During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days).
Occurrence of Platelet Transfusions
Percentage of patients requiring a platelet transfusion
Measured: During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days).
Occurrence of Febrile Neutropenia Adverse Events
Percentage of patients who experience febrile neutropenia adverse events
Measured: During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days).
Occurrence of Infection Serious Adverse Events (SAEs)
Percentage of patients experiencing an SAE that codes to the Medical Dictionary for Regulatory Activities (MedDRA) system organ class (SOC) of Infections and Infestations
Measured: During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days).
Occurrence of Pulmonary Infection Serious Adverse Events (SAEs)
Percentage of patients experiencing an SAE that codes to the Medical Dictionary for Regulatory Activities (MedDRA) system organ class (SOC) of Infections and Infestations and falls into a preferred term (PT) categorized as a pulmonary infection custom MedDRA query (CMQ)
Measured: During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days).
Dose Reductions in Chemotherapy (Topotecan)
Overall event rate of dose reductions in chemotherapy (topotecan)
Measured: During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days).
Occurrence of Grade 3 and 4 Hematologic Toxicities
The count of patients with any hematologic lab value that meets the CTCAE toxicity grade criteria for ≥ Grade 3 and the value is treatment emergent (occurs after first dose of study drug). Labs include: Hemoglobin (HGB), hematocrit, white blood cell (WBC), platelet counts, ANC, ALC, Monocyte Absolute, Basophil Absolute, and Eosinophil Absolute.
Measured: During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days).
Occurrence of Grade 4 and Grade 3/4 Decreased Platelet Count Laboratory Values (Thrombocytopenia)
The count of patients with any platelet lab value that meets the CTCAE toxicity grade criteria for ≥ Grade 3 and the value is treatment emergent (occurs after first dose of study drug).
Measured: During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days).
Occurrence of Erythropoietin-stimulating Agent (ESA) Administrations
The count of patients who received any ESA administration.
Measured: During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days).
Chemotherapy Exposure
Average duration of exposure to chemotherapy (topotecan) in days.
Measured: During the treatment period. From date of first dose, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to a maximum of 1335 days).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Aug 2015 (estimated)
- Study start5 Oct 2015
- Primary completion28 Sep 2018
- Study completion4 Oct 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Small Cell Lung CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 123 participants (actual)
Sponsor and investigators
- Lead sponsor
- G1 Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Contact, Study director, G1 Therapeutics, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02514447
- Sponsor's protocol ID
- G1T28-03
- Other IDs
- 2016-004611-13, 2016
- Status last verified
- Sep 2025
- First submitted
- 31 Jul 2015
- Last updated
- 25 Sep 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Hart LL, Ferrarotto R, Andric ZG, Beck JT, Subramanian J, Radosavljevic DZ, Zaric B, Hanna WT, Aljumaily R, Owonikoko TK, Verhoeven D, Xiao J, Morris SR, Antal JM, Hussein MA. Myelopreservation with Trilaciclib in Patients Receiving Topotecan for Small Cell Lung Cancer: Results from a Randomized, Double-Blind, Placebo-Controlled Phase II Study. Adv Ther. 2021 Jan;38(1):350-365. doi: 10.1007/s12325-020-01538-0. Epub 2020 Oct 29.
PubMed 33123968Li C, Horton JK, Sale M, Curd L, Goti V, Tao W, Beelen A. Pharmacokinetic Drug-Drug Interaction Studies Between Trilaciclib and Midazolam, Metformin, Rifampin, Itraconazole, and Topotecan in Healthy Volunteers and Patients with Extensive-Stage Small-Cell Lung Cancer. Clin Drug Investig. 2022 Aug;42(8):679-692. doi: 10.1007/s40261-022-01179-x. Epub 2022 Jul 16.
PubMed 35842567Hussein M, Maglakelidze M, Richards DA, Sabatini M, Gersten TA, Lerro K, Sinielnikov I, Spira A, Pritchett Y, Antal JM, Malik R, Beck JT. Myeloprotective Effects of Trilaciclib Among Patients with Small Cell Lung Cancer at Increased Risk of Chemotherapy-Induced Myelosuppression: Pooled Results from Three Phase 2, Randomized, Double-Blind, Placebo-Controlled Studies. Cancer Manag Res. 2021 Aug 9;13:6207-6218. doi: 10.2147/CMAR.S313045. eCollection 2021.
PubMed 34408488Ferrarotto R, Anderson I, Medgyasszay B, Garcia-Campelo MR, Edenfield W, Feinstein TM, Johnson JM, Kalmadi S, Lammers PE, Sanchez-Hernandez A, Pritchett Y, Morris SR, Malik RK, Csoszi T. Trilaciclib prior to chemotherapy reduces the usage of supportive care interventions for chemotherapy-induced myelosuppression in patients with small cell lung cancer: Pooled analysis of three randomized phase 2 trials. Cancer Med. 2021 Sep;10(17):5748-5756. doi: 10.1002/cam4.4089. Epub 2021 Aug 18.
PubMed 34405547Li C, Hart L, Owonikoko TK, Aljumaily R, Rocha Lima CM, Conkling PR, Webb RT, Jotte RM, Schuster S, Edenfield WJ, Smith DA, Sale M, Roberts PJ, Malik RK, Sorrentino JA. Trilaciclib dose selection: an integrated pharmacokinetic and pharmacodynamic analysis of preclinical data and Phase Ib/IIa studies in patients with extensive-stage small cell lung cancer. Cancer Chemother Pharmacol. 2021 May;87(5):689-700. doi: 10.1007/s00280-021-04239-9. Epub 2021 Feb 17.
PubMed 33595690
Study at a glance
From the registry record, last updated by the sponsor on 25 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1b/2a Safety and Pharmacokinetic Study of G1T28 in Patients With Previously Treated Extensive Stage Small Cell Lung Cancer (SCLC) Receiving Topotecan Chemotherapy
- ClinicalTrials.gov ID
- NCT02514447
- Acronym / sponsor ID
- G1T28-03
- Conditions
- Small Cell Lung Cancer
- Keywords
- SCLC, CDK4/6 Inhibitor
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 123 participants (actual)
- Lead sponsor
- G1 Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- 5 Oct 2015 (actual)
- Primary completion
- 28 Sep 2018 (actual)
- Study completion
- 4 Oct 2021 (actual)
- First posted
- 3 Aug 2015 (estimated)
- Results
- Posted 9 Jun 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This was a study to investigate the potential clinical benefit of trilaciclib (G1T28), a Cyclin Dependent Kinase (CDK) 4/6 inhibitor, in preserving the bone marrow and the immune system, in order to decrease chemotherapy-induced myelosuppression and improve anti-tumor efficacy when administered prior to topotecan in patients previously treated for extensive-stage SCLC.
The study consisted of 2 parts: a limited open-label, dose-finding portion (Part 1), and a randomized double-blind portion (Part 2). Both parts included 3 study phases: Screening Phase, Treatment Phase, and Survival Follow-up Phase. The Treatment Phase began on the day of first dose with study treatment and completes at the Post-Treatment Visit.
Detailed description
Overall, up to 130 patients were planned to be enrolled in the study. In Part 1, approximately 40 patients were planned to be enrolled, assuming 9 to 10 cohorts. Part 1 was open-label, and no randomization or blinding was required. In Part 2A, approximately 45 patients were to be enrolled and randomly assigned (2:1) to trilaciclib (240 mg/m2) and topotecan (0.75 mg/m2) or placebo and topotecan (1.5 mg/m2). In Part 2B, approximately 45 patients were to be enrolled and randomly assigned (2:1) to trilaciclib (240 mg/mg2) and topotecan (1.5 mg/m2) or placebo and topotecan (1.5 mg/m2).
Patients who received placebo in Part 2A and Part 2B were to be combined into a single placebo group for the analysis to compare with trilaciclib+topotecan 1.5 mg/m2 with placebo + topotecan 1.5 mg/m2 (proximately 30 per treatment group).
The sample size calculation was to demonstrate the superiority of trilaciclib + topotecan 1.5 mg/m2 over placebo + topotecan 1.5 mg/m2 with respect to at least 1 of the primary endpoints. The overall type I error rate was 1-sided 0.10. Using the most conservative Bonferroni procedure for the 2 primary endpoints, a 1-sided individual type I error rate 0.10/2=0.05 was assigned to each outcome variable (DSN in Cycle 1 and occurrence of SN) in the sample size calculation. Assuming a common standard deviation of 2.5, a difference in the duration of SN in Cycle 1 of at least 2 days between the treatment groups, a sample size of 28 per arm was required to have 90% power to detect the assumed treatment effect. For occurrence of SN, assuming the event rate was 45% for placebo group, to detect an absolute reduction of 37% by trilaciclib group with 90% power would require a sample size of at least 29 per arm. Thus, 30 per arm was needed to ensure 90% power to detect assumed treatment effect for DSN in Cycle 1 and occurrence of SN. All calculations were carried out using the POWER procedure in SAS®, Version 9.4 procedure in SAS®, Version 9.4 or higher.
The results from endpoints that were commonly collected at Part 1 and part 2 are presented together in this report.
The posted results represent the final results of Study G1T28-03, a Phase 1b/2a safety and pharmacokinetic (PK) study of trilaciclib (G1T28) in patients with previously treated extensive-stage small cell lung cancer (SCLC) receiving topotecan chemotherapy in the second/third-line (2/3L) setting. The final myelopreservation efficacy results for both parts and exposure for Part 1 are from database lock 1 (data cut-off [DCO] for Primary Completion Date [PCD] 28 September 2018). The final anti-tumor efficacy (BOR, DOR, PFS) for both parts, final overall survival for Part 1 and exposure data from Part 2 are from a second database lock 2 (DCO 31 May 2019) and the final overall survival for Part 2 and safety (adverse events) are through the end of the study on October 4, 2021 which resulted in the final database lock (DCO 01 Nov 2021).
The maximum time frames provided reflect the time from when the first patient could be evaluated for an endpoint (ie. date of first dose of first patient) to the time when the data from both parts presented for that endpoint was considered final.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 9
| Arm | Type | Receives |
|---|---|---|
| Placebo + Topotecan 1.5 mg/m² - Parts 2a and 2b | Experimental | Drug: Placebo, Drug: TopotecanPatients in Parts 2a and 2b were randomized 1:2 to placebo. Patients received placebo administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of placebo on Days 1 to 5, patients received IV topotecan (1.5 mg/m²). |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Part 2a | Experimental | Drug: Trilaciclib, Drug: TopotecanPatients in Part 2a were randomized 2:1 to trilaciclib. Patients received trilaciclib (240 mg/m²) administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.5 mg/m² - Part 2b | Experimental | Drug: Trilaciclib, Drug: TopotecanPatients in Part 2b were randomized 2:1 to trilaciclib. Patients received trilaciclib (240 mg/m²) administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.5 mg/m²). |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.5 mg/m² - Cohort 1- Part 1 | Experimental | Drug: Trilaciclib, Drug: TopotecanPatients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.50 mg/m²). |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.25 mg/m² - Cohort 2- Part 1 | Experimental | Drug: Trilaciclib, Drug: TopotecanPatients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.25 mg/m²). |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 0.75 mg/m² - Cohort 3- Part 1 | Experimental | Drug: Trilaciclib, Drug: TopotecanPatients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Cohorts 4 and 6- Part 1 | Experimental | Drug: Trilaciclib, Drug: TopotecanPatients received trilaciclib (240 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). |
| Trilaciclib (G1T28) 280 mg/m² + Topotecan 0.75 mg/m² - Cohort 5- Part 1 | Experimental | Drug: Trilaciclib, Drug: TopotecanPatients received trilaciclib (280 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.0 mg/m² - Cohort 7- Part 1 | Experimental | Drug: Trilaciclib, Drug: TopotecanPatients received trilaciclib (240 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.0 mg/m²). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Male or female subjects aged ≥18 years
- Confirmed diagnosis of SCLC by histology or cytology, preferably including the presence of neuroendocrine features by immunohistochemistry
- Progression during or after prior first- or second-line chemotherapy and eligible to receive topotecan therapy
- At least 1 target lesion that is measurable by RECIST, Version 1.1
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2
Key exclusion criteria (7 listed)
- Presence of brain metastases requiring immediate treatment with radiation therapy or steroids.
- Uncontrolled ischemic heart disease or uncontrolled symptomatic congestive heart failure
- Known history of stroke or cerebrovascular accident within 6 months prior to enrollment
- Other uncontrolled serious chronic disease or conditions that in the investigator's opinion could affect compliance or follow-up in the protocol
- Concurrent radiotherapy to any site or radiotherapy within 2 weeks prior to enrollment or previous radiotherapy to the target lesion sites
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TrilaciclibAlso: G1T28, CDK 4/6 inhibitor | Drug | Trilaciclib (G1T28) 200 mg/m² + Topotecan 0.75 mg/m² - Cohort 3- Part 1, Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.25 mg/m² - Cohort 2- Part 1, Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.5 mg/m² - Cohort 1- Part 1, Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Cohorts 4 and 6- Part 1, Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Part 2a, Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.0 mg/m² - Cohort 7- Part 1, Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.5 mg/m² - Part 2b, Trilaciclib (G1T28) 280 mg/m² + Topotecan 0.75 mg/m² - Cohort 5- Part 1 |
| Placebo | Drug | Placebo + Topotecan 1.5 mg/m² - Parts 2a and 2b |
| Topotecan | Drug | Placebo + Topotecan 1.5 mg/m² - Parts 2a and 2b, Trilaciclib (G1T28) 200 mg/m² + Topotecan 0.75 mg/m² - Cohort 3- Part 1, Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.25 mg/m² - Cohort 2- Part 1, Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.5 mg/m² - Cohort 1- Part 1, Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Cohorts 4 and 6- Part 1, Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Part 2a, Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.0 mg/m² - Cohort 7- Part 1, Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.5 mg/m² - Part 2b, Trilaciclib (G1T28) 280 mg/m² + Topotecan 0.75 mg/m² - Cohort 5- Part 1 |
Primary outcome
Duration of Severe (Grade 4) Neutropenia in Cycle 1
Time frame: Evaluated for Cycle 1 (i.e., from date of first dose of study drug (Part 1)/randomization (Part 2) to the end of Cycle 1, each cycle = 21 days)
Duration of severe neutropenia (DSN; days) was defined as the number of days from the date of the first ANC value of <0.5 × 10^9/L observed between start of cycle and end of cycle to the date of the first ANC value ≥0.5 × 10^9/L that met the following criteria: (1) occurred after the ANC value of <0.5 × 10^9/L and (2) no other ANC values <0.5 × 10^9/L occurred between this day and end of cycle. DSN is set to 0 for patients who did not experience SN in a cycle, including those who were randomized but never treated. Data from unscheduled visits and the actual assessment date (rather than visit date) were included in the derivation.
Occurrence of Severe (Grade 4) Neutropenia
Time frame: During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days).
Number of Participants with severe (Grade 4) neutropenia (SN) was a binary variable. If a patient had at least 1 absolute neutrophil count value <0.5 × 10^9/L during the Treatment Period, the patient was assigned as Yes to the occurrence of SN; otherwise, it was No.
Assess the Dose Limiting Toxicities (DLTs) of G1T28/Trilaciclib Administered With Topotecan in Part 1
Time frame: Evaluated for Cycle 1 (i.e., from date of first dose of study drug (Part 1) to the end of Cycle 1, each cycle = 21 days)
The percentage of patients experiencing DLTs in Part 1 of the study in each cohort, including: * Absolute neutrophil count (ANC) < 0.5 × 10^9/L lasting for ≥ 7 days * ≥ Grade 3 neutropenic infection/febrile neutropenia * Grade 4 thrombocytopenia or ≥ Grade 3 thrombocytopenia with bleeding * Unable to start next cycle of chemotherapy due to lack of recovery to an ANC ≥ 1.5 × 10^9/L and platelet count ≥ 100 × 10^9/L; a delay of up to 1 week from the scheduled start of Cycle 2 is allowed for recovery of ANC and platelet count, and is not considered a DLT * ≥ Grade 3 nonhematologic toxicity (nausea, vomiting, and diarrhea failing maximal medical management; fatigue lasting for > 72 hours)
20 secondary outcomes
Pharmacokinetic Profile for Trilaciclib (G1T28) When Administered With Topotecan
Time frame: Part 1 of the study during Cycle 1 Day 4 : predose, 0.5, 1, 1.5, 2, 2.5, 3, 4.5, 6.5, 8.5 (optional), and 24.5 hours post dose. Part 2 of the study during Cycle 1 Day 4 : predose, 0.5, 1, between 3 to 4 hours and between 5.5 to 6.5 hours post dose.
Progression Free Survival (PFS)
Time frame: From date of first dose of study drug (Part 1)/randomization (Part 2), until date of documented disease progression or death due to any cause (evaluated up to a maximum of 1335 days).
Overall Survival (OS)
Time frame: From date of first dose of study drug (Part 1)/randomization (Part 2) until the date of death due to any cause (evaluated up to a maximum of 2220 days).
Assess the Hematologic Profile of G1T28/Trilaciclib Administered With Topotecan
Time frame: During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days).
Tumor Response Based on RECIST, Version 1.1
Time frame: From date of first dose of study drug (Part 1)/randomization (Part 2) until the occurrence of progressive disease, withdrawal of consent, or initiation of subsequent anti-cancer therapy, (assessed up to a maximum of 1335 days).
Occurrence of RBC Transfusions
Time frame: During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1056 days).
Need for Treatment With Hematopoietic Growth Factors
Time frame: During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days).
Chemotherapy Cycles and Modifications Overall
Time frame: During the treatment period. From date of first dose, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to a maximum of 1335 days).
Pharmacokinetic Profile for Topotecan When Administered With Trilaciclib (G1T28)
Time frame: Part 1 of the study during Cycle 1 Day 4 : predose, 0.5, 1, 1.5, 2, 2.5, 3, 4.5, 6.5, 8.5 (optional), and 24.5 hours post dose. Part 2 of the study during Cycle 1 Day 4 : predose, 0.5, 1, between 3 to 4 hours and between 5.5 to 6.5 hours post dose.
Duration of Response (DOR)
Time frame: From date of first dose of study drug (Part 1)/randomization (Part 2) until the occurrence of progressive disease, withdrawal of consent, or initiation of subsequent anti-cancer therapy, (assessed up to a maximum of 1335 days).
Occurrence of Intravenous (IV) Antibiotic Use
Time frame: During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days).
Occurrence of Platelet Transfusions
Time frame: During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days).
Occurrence of Febrile Neutropenia Adverse Events
Time frame: During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days).
Occurrence of Infection Serious Adverse Events (SAEs)
Time frame: During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days).
Occurrence of Pulmonary Infection Serious Adverse Events (SAEs)
Time frame: During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days).
Dose Reductions in Chemotherapy (Topotecan)
Time frame: During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days).
Occurrence of Grade 3 and 4 Hematologic Toxicities
Time frame: During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days).
Occurrence of Grade 4 and Grade 3/4 Decreased Platelet Count Laboratory Values (Thrombocytopenia)
Time frame: During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days).
Occurrence of Erythropoietin-stimulating Agent (ESA) Administrations
Time frame: During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days).
Chemotherapy Exposure
Time frame: During the treatment period. From date of first dose, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to a maximum of 1335 days).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Sep 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 33123968Hart LL, Ferrarotto R, Andric ZG, Beck JT, Subramanian J, Radosavljevic DZ, Zaric B, Hanna WT, Aljumaily R, Owonikoko TK, Verhoeven D, Xiao J, Morris SR, Antal JM, Hussein MA. Myelopreservation with Trilaciclib in Patients Receiving Topotecan for Small Cell Lung Cancer: Results from a Randomized, Double-Blind, Placebo-Controlled Phase II Study. Adv Ther. 2021 Jan;38(1):350-365. doi: 10.1007/s12325-020-01538-0. Epub 2020 Oct 29.
- Derived from this study: PubMed 35842567Li C, Horton JK, Sale M, Curd L, Goti V, Tao W, Beelen A. Pharmacokinetic Drug-Drug Interaction Studies Between Trilaciclib and Midazolam, Metformin, Rifampin, Itraconazole, and Topotecan in Healthy Volunteers and Patients with Extensive-Stage Small-Cell Lung Cancer. Clin Drug Investig. 2022 Aug;42(8):679-692. doi: 10.1007/s40261-022-01179-x. Epub 2022 Jul 16.
- Derived from this study: PubMed 34408488Hussein M, Maglakelidze M, Richards DA, Sabatini M, Gersten TA, Lerro K, Sinielnikov I, Spira A, Pritchett Y, Antal JM, Malik R, Beck JT. Myeloprotective Effects of Trilaciclib Among Patients with Small Cell Lung Cancer at Increased Risk of Chemotherapy-Induced Myelosuppression: Pooled Results from Three Phase 2, Randomized, Double-Blind, Placebo-Controlled Studies. Cancer Manag Res. 2021 Aug 9;13:6207-6218. doi: 10.2147/CMAR.S313045. eCollection 2021.
- Derived from this study: PubMed 34405547Ferrarotto R, Anderson I, Medgyasszay B, Garcia-Campelo MR, Edenfield W, Feinstein TM, Johnson JM, Kalmadi S, Lammers PE, Sanchez-Hernandez A, Pritchett Y, Morris SR, Malik RK, Csoszi T. Trilaciclib prior to chemotherapy reduces the usage of supportive care interventions for chemotherapy-induced myelosuppression in patients with small cell lung cancer: Pooled analysis of three randomized phase 2 trials. Cancer Med. 2021 Sep;10(17):5748-5756. doi: 10.1002/cam4.4089. Epub 2021 Aug 18.
- Derived from this study: PubMed 33595690Li C, Hart L, Owonikoko TK, Aljumaily R, Rocha Lima CM, Conkling PR, Webb RT, Jotte RM, Schuster S, Edenfield WJ, Smith DA, Sale M, Roberts PJ, Malik RK, Sorrentino JA. Trilaciclib dose selection: an integrated pharmacokinetic and pharmacodynamic analysis of preclinical data and Phase Ib/IIa studies in patients with extensive-stage small cell lung cancer. Cancer Chemother Pharmacol. 2021 May;87(5):689-700. doi: 10.1007/s00280-021-04239-9. Epub 2021 Feb 17.
- Myelopreservation with Trilaciclib in Patients Receiving Topotecan for Small Cell Lung Cancer: Results from a Randomized, Double-Blind, Placebo-Controlled Phase II StudyLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Contact study director
G1 Therapeutics, Inc.
50 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Trilaciclib and Topotecan in people with Small Cell Lung Cancer, run by G1 Therapeutics, Inc. at 50 sites in 8 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 50 sites in United States, Serbia, Croatia, Bosnia and Herzegovina, Slovakia and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Jun 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Duration of Severe (Grade 4) Neutropenia in Cycle 1 (time frame: Evaluated for Cycle 1 (i.e., from date of first dose of study drug (Part 1)/randomization (Part 2) to the end of Cycle 1, each cycle = 21 days)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02514447, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Sep 2025.